Spring 20021

Lecture # 1: Course Introduction

•I. Instructor and Background–

Dr. Richard Kuhn–

rjkuhn@bragg.bio.purdue.edu

–B-129 Lilly Hall

–494-1164

–O

ffice Hours - Wednesday 10:30 - 11:30

•II. O

bjective: To use viruses as a vehicle to:–

1) Study disease–

2) Examine how viruses provide ideal m

odel systems for unraveling how the

cell itself functions.–

3) Demonstrate the potential of using viruses to deliver genes and other novel

therapeutic approaches

•III. W

hat are the requirements for taking and passing this course?

–1) Core biology courses

–2) The ability to blend fundam

ental principles from biology, chem

istry, andphysics

–3) A little curiosity and som

e work

Spring 20022

•IV. Course syllabus:

–1. Course lim

ited to eukaryotic host-viral systems

–2. Two different phases to the course:

•a) Introduction to viral processes

•b) An exam

ination of specific viral systems

•V. Description of class m

echanics–

1. Lecture format:

•a. Lecture with research exam

ples•

b. Straight mem

orization will not help you: apply principles!•

c. Ask questions or I will ask questions of you–

2. Texts•

Viruses and Human Disease (Strauss & Strauss) 2002

•Fundam

entals of Molecular Virology (Acheson) 2002

•Reference: Principles of Virology (Flint, Enquist, Krug, Racaniello, Skalka) 1999 -Not required but good reading and diagram

s–

3. Lecture notes: will be available as PDFs on the web.–

4. Exams: 3 exam

s equal weight (33% each exam

).•

a. Final is not cumulative (covers only last 1/3)

•b. Form

at of exams: short answer/ T/F/ thinking essays

•c. Approach to passing exam

s: apply principles

Spring 20023

Spring 20024

5IN

TR

OD

UC

TIO

N

“the p

ox”

1798

Jenner

6IN

TR

OD

UC

TIO

N

Infective

Bacteria-F

reeF

iltrate

1798

Jenner

1890

Iwanow

ski,B

eijerinck,Loeffler &F

rosch

Spring 20027

Early Discovery of Infectious A

gents

Spring 20028

Early Landmarks in V

irus ResearchD

ateV

irologistD

iscovery

late 1800’s K

ochFilterable agents, K

och’s postulates

1898Loeffler &

FroschFirst dem

onstration of a filterable animal virus, foot and m

outh virus

1901Reed

Identification of Yellow

fever virus

1909 Landsteiner &

Popper

Transmission of CN

S fluid from child to m

onkey establishes a virus as a causative agent for poliom

yelitis

1911Rous

Identified virus causing solid tumors, Rous sarcom

a virus

1931W

oodruffU

se of embryonic hen’s egg as a viral host

1933Sm

ithIsolation of Influenza

1949Enders

Nonneuronal tissue supports poliovirus replication in culture

1952D

ulbeccoD

evelopment of virus plaque assay

1952H

ershey & Chase

Nucleic acid is the genetic m

aterial

1950sSalk &

SabinD

evelopment of killed and attenuated poliovirus vaccines

1972Tem

in & Baltim

oreD

iscovery of reverse transcriptase

1984M

ontagnier & G

alloIsolation of H

IV as the causative agent for A

IDS

Spring 20029

YearN

ames

Nobel C

itation; Virus Group or Fam

ily

1946[Chem

istry]W

endell StanleyIsoation, purification and crystallization of tobacco m

osaic virus; Tobam

ovirus

1980 [Chem

istry]Paul Berg

Studies of the biochemistry of nucleic acids, w

ith particular regard to recom

binant DN

A (SV40);Polyom

aviridae

1982[Chem

sitry]A

aron KlugD

evelopment of crystallographic electron m

icroscopy and structural elucidation of biologically im

portant nucleic acid- protein com

plexes;Tobamovirus and Tym

ovirus

1951M

ax TheilerD

evelopment of yellow

fever vaccine; Flaviviridae

1954John F. Enders,Thom

as Weller,

Frederick C. Robbins

Grow

th and cultivation of poliovirus; Picornaviridae

1958Joshua Lederberg

Transforming bacteriophages

1965Francois Jacob,A

ndré Lwoff

Jacques Monod

Operons; bacteriophages

1966Francis Peyton Rous

Discovery of tum

or-producing viruses; Retroviridae

1969M

ax Delbruck,

Alfred D

. Hershey,

Salvador E. Luria

Mechanism

of virus infection in living cells; bacteriophages

1975D

avid Baltimore,

How

ard M. Tem

in,Renato D

ulbecco

Discoveries concerning the interaction betw

een tumour

viruses and the genetic material of the cell; Retroviridae

1976D

. Carleton Gajdusek

Baruch S. Blumberg

New

mechanism

s for the origin and dissemination of

infectious diseases; B with H

epadnaviridae, G w

ith prions.

1989J. M

ichael Bishop,H

arold E. Varmus

Discovery of the cellular origin of retroviral oncogenes;

Retroviridae

1993Phillip A

. SharpRichard J. Roberts

Discoveries of split (spliced) genes; A

denoviridae

1988G

eorge Hitchings

Gertrude Elion

Important principles of drug treatm

ent using nucleotide analogs (acyclovir)

1996Rolf ZinkernagelPeter D

ohertyPresentation of viral epitopes by M

HC

1997Stanley Prusiner

Prions

Nobel Prizes involving V

irology *

*A

ll prizes listed are in Physiology or Medicine except those three m

arked [Chemistry].

1978A

pplication of restriction endonucleases to the study of the genetics of SV40; Polyom

aviridaeD

aniel Nathans

****

**In these tw

o instances, the prize was shared w

ith unlisted recipients whose w

ork did not involve viruses.

Spring 200210

Spring 200211

Properties of Viruses

•A

. Definitions:

1.O

bligate intracellular parasites with a relatively sim

ple life cycle and/or2.

Viruses are entities w

hose genomes (nucleic acids) replicate inside living cells using

the cellular biosynthetic machinery and cause the synthesis of specialized elem

ents(virions) that can transfer the viral genom

e to other cells.

•B.

Small in size—

can pass through bacteriological filters

•C

. Viruses contain no enzym

es used for energy production. Some do contain

enzymes associated w

ith nucleic acid metabolism

.

•D

.V

iruses contain only one type of nucleic acid.–

1 .RN

A, double stranded or single stranded.

–2 .

DN

A, double stranded or single stranded.

–3 .

Nucleic acid is m

ain component of virion (plus coat)

–4 .

Some viruses have enzym

es in virion particles.

•E.

Replicate through an “assembly-line’ like m

echanism in the host cell—

use host cellm

etabolic machinery to synthesize all of the necessary viral com

ponents and then assemble

them into virus particle - sim

ple nature of life cycle compared to that of a eukaryotic cell.

Spring 200212

Properties of Viruses (cont’d)

•F. V

iruses known to infect nearly all organism

s.–

1. Bacteria - bacteriophages.–

2. Plants - RNA

or DN

A containing viruses as w

ell as agents called viroids.–

3. Insects - numerous viruses infect insects; certain viruses are transm

itted to bothplants and anim

als via insect vectors.–

4. Higher anim

als

Spring 200213

Levels of Analysis:

•M

olecular:»

Cell Biology»

Biochemistry

»G

enetics»

Structure

•Clinical (organism

): Pathogenesis- disease patterns- organs and tissues affected- im

mune response

•Population G

roups: Epidemiological

Spring 200214

The study of viruses require:

•1) Isolate virus and quantitate

•2) Propagate and m

anipulate–

a. animal m

odel–

replication and pathogenesis–

b. cell culture–

replication and genetics

•3) In vitro biochem

istry–

a. develop enzymatic assays

–b. study virus assem

bly–

c. determine three-dim

ensional structure of virus–

particle and viral proteins

Spring 200215

Scale of Viruses

16C

LAS

SIF

ICA

TIO

N

+ m

RN

A

- RN

A V

RN

A+-

III

+ o

r - DN

AII

DN

A+-

I

+ R

NA

- RN

AIV

+ R

NA

DN

AV

I

17C

LAS

SIF

ICA

TIO

N

+ m

RN

A

RE

TR

OV

IRID

AE

PA

RV

OV

IRID

AE

RE

OV

IRID

AE

PIC

OR

NA

VIR

IDA

ET

OG

AV

IRID

AE

FL

AV

IVIR

IDA

EC

AL

ICIV

IRID

AE

CO

RO

NA

VIR

IDA

E

BU

NY

AV

IRID

AE

AR

EN

AV

IRID

AE

RH

AB

DO

VIR

IDA

EP

AR

AM

YX

OV

IRID

AE

OR

TH

OM

YX

OV

IRID

AE

HE

PA

DN

AV

IRID

AE

PA

PO

VA

VIR

IDA

EA

DE

NO

VIR

IDA

EH

ER

PE

SV

IRID

AE

PO

XV

IRID

AE

- RN

A V

RN

A+-

III

+ o

r - DN

AII

DN

A+-

I

+ R

NA

- RN

AIV

+ R

NA

DN

AV

I

Spring 200218

Classification Scheme for A

nimal RN

A V

iruses

Spring 200219

Classification Scheme for A

nimal D

NA

Viruses

Spring 200220

Web Sites of Interest to V

irologists

•1.

http://ww

w.tulane.edu/~dm

sander/garryfavweb.htm

l–

(Has links to alm

ost all the virology sites on the web)

•2.

http://boris.qub.ac.uk/vsd/vsd6d.html

•3.

http://bilbo.bio.purdue.edu/~virusww

w/

•4.

http://ww

w.bocklabs.w

isc.edu/welcom

e.html

•5.

http://life.anu.edu.au:80/viruses/indxvir2.htm•

(A list of ICTV-approved virus names and links to virus databases)

•6.

http://life.anu.edu.au:80//./viruses/virus.html